التفاصيل البيبلوغرافية
| العنوان: |
Integration of metabolomics and fluxomics via nonequilibrium thermodynamics |
| المؤلفون: |
Park, Junyoung O. |
| المساهمون: |
Rabinowitz, Joshua D, Chemical and Biological Engineering Department |
| بيانات النشر: |
Princeton University |
| سنة النشر: |
2016 |
| المجموعة: |
DataSpace at Princeton University |
| مصطلحات موضوعية: |
Enzyme efficiency, Mass spectrometry, Metabolic flux analysis, Metabolism, Systems biology, Thermodynamics, Biochemistry, Chemical engineering, Analytical chemistry |
| الوصف: |
Metabolism is the process of converting nutrients into usable energy (e.g., ATP) and biomass building blocks (e.g., amino acids, nucleotides, and lipids). The biochemistry of metabolic reactions and the structure of metabolic networks bear impressive resemblance across widely divergent organisms. Like all chemical networks, metabolism must obey the second law of thermodynamics: each pathway step must generate entropy and cost free energy (ΔG). As available free energy is limited, a fundamental challenge is partitioning the requisite free energy loss across pathway steps. For each reaction, ΔG is log-proportional both to a concentration ratio (reaction quotient-to-equilibrium constant) and to a flux ratio (backward-to-forward flux). With 13C isotope labeling, absolute metabolite concentrations and fluxes can be measured in various cell types and organisms including E. coli, yeast, and mammalian cells. Then, the concentration and flux ratios can be integrated via ΔG using the non-equilibrium thermodynamic principle. The integrative analysis yields internally consistent and comprehensive sets of metabolite concentrations and ΔG in each organism. In glycolysis, free energy is partitioned so as to mitigate unproductive backwards fluxes associated with ΔG near zero. Across metabolism, absolute metabolite concentrations and ΔG are substantially conserved such that most substrate (but not inhibitor) concentrations exceed the associated enzyme binding site affinity. The observed conservation of metabolite concentrations may reflect an evolutionary drive to simultaneously satisfy thermodynamic constraints and efficiently utilize enzyme active sites. Modulation of metabolic fluxes allows cells to meet their energetic and material demand in various conditions. In pathway upregulation, cells must coordinate the pathway steps as any one reaction may become limiting. A combination of 2H and 13C labeling reveals the extent of reversibility of glycolytic reactions. In E. coli, glycolysis under nitrogen limitation is ... |
| نوع الوثيقة: |
doctoral or postdoctoral thesis |
| اللغة: |
English |
| العلاقة: |
The Mudd Manuscript Library retains one bound copy of each dissertation. Search for these copies in the library's main catalog: http://catalog.princeton.eduTest/; http://arks.princeton.edu/ark:/88435/dsp01mw22v787wTest |
| الإتاحة: |
http://arks.princeton.edu/ark:/88435/dsp01mw22v787wTest |
| رقم الانضمام: |
edsbas.4B6737C6 |
| قاعدة البيانات: |
BASE |
